I. Field of the Invention
In response to contact with antigens through various allergen mediators, hypersensitive individuals exhibit an altered physiological state resulting in the formation of antigen-specific antibodies. Subsequent contact with one or more of said antigens or a structurally similar substance can evoke, in an allergic individual, various physical responses ranging from minor discomforts such as urticaria and eczema to pathological manifestations such as bronchial asthma.
Allergic responses are involved with the production within an individual of a type of tissue-sensitizing IgE antibody called a reagin. These IgE antibodies have a high affinity for receptors on cells present in various body tissues. The receptors are on mast cells which are found in close association with capillaries in connective tissues throughout the body and on basophilic leukocytes (blood cells). Mast cells and basophils contain a high content of pharmacologically-active mediators or spasmogens, such as histamine, serotonin (5-hydroxytryptamine) and kinins (basic peptides) which are concentrated in cytoplasmic granules. Contact of the IgE antibodies (which are fixed to mast cells and basophils) with antigens can trigger cross-linking of the IgE antibodies. In turn, this cross-linking causes degranulation of mast cells and basophils, which releases the chemical mediators and produces manifestations of the allergic response, e.g., bronchial asthma referred to earlier. In order to reduce the undesirable allergic response, it has been suggested to administer various compounds which have an antiallergic characteristic of interfering with the degranulation of mast cells and basophils.
Antiallergic compounds are often administered parenterally, which involves inconvenience to the patient. There is a need for antiallergic compounds having increased efficacy over known compounds, especially compounds which are orally active.
II. Description of Pertinent Art
U.S. Pat. No. 4,221,800 discloses substituted cycloalkenochromones. Preferred compounds are substituted in the 6 or 7-position. Preferred 6 or 7-substituents are tetrazoyl, methylthio, methylsulfonyl or methylsulfinyl. There is no disclosure of the antiallergenic activity of 5-oxamate-substituted chromones or thiochromones.
U.S. Pat. No. 4,290,954 discloses a large series of cycloalkenochromones; none of the compounds disclosed are 5-oxamates. G.B. Pat. No. 1,561,731 discloses 6 and 7-substituted chromones; 5-oxamate chromones or thiochromones are not described.